Pablo Sackmann

Fil: López, Hugo Luis. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Vertebrados; ArgentinaFil: Bastida, Ricardo. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Vertebrados; ArgentinaFil: Bonetti, S.. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Vertebrados; ArgentinaFil: Rouaux, Julia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Zoología Vertebrados; Argentin

Miristato de miristilo “100% natural”. Estudio del proceso de síntesis biocatalítica

El miristato de miristilo es uno de los ésteres cerosos másutilizados en las formulaciones cosméticas como emoliente.La legislación europea permite catalogar como productosnaturales a todos aquellos obtenidos directamente dela naturaleza o los sintetizados mediante procedimientosbiocatalíticos. En este contexto, el presente trabajo recogelos estudios realizados para optimizar la síntesis biocatalíticade miristato de miristilo con lipasa de Candida antarcticainmovilizada (Novozym® 435). Operando a 70ºC, avacío y con circulación de N2 seco, se ha podido obtener,en tan sólo 2 horas, un éster que presenta las mismas características (número ácido, valor de hidroxilo, índice deyodo e índice de saponificación), que los productos quese encuentran actualmente en el mercado, con la notableventaja de que este miristato de miristilo permite el etiquetadode los productos cosméticos que lo contienen como“100% natural”

Dual EGFR inhibition in combination with anti-VEGF treatment in colorectal cancer.

Preclinical studies demonstrate that epidermal growth factor receptor (EGFR) signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic. We conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with metastatic colorectal cancer was analyzed for safety and antitumor activity. Forty-one patients with heavily pretreated metastatic colorectal cancer received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (68%), hypomagnesemia (37%), and fatigue (15%). Thirty of 34 patients (88%) treated at the full FDA-approved doses of all three drugs tolerated treatment without drug-related dose-limiting effects. Eleven patients (27%) achieved stable disease (SD) ≥6 months and three (7%) achieved a partial response (PR) (total SD>6 months/PR= 14 (34%)). Of the 14 patients with SD≥6 months/PR, eight (57%) had received prior sequential bevacizumab and cetuximab, two (5%) had received bevacizumab and cetuximab concurrently, and four (29%) had received prior bevacizumab but not cetuximab or erlotinib (though three had received prior panitumumab). The combination of bevacizumab, cetuximab, and erlotinib was well tolerated and demonstrated antitumor activity in heavily pretreated patients with metastatic colorectal cancer

Dual EGFR inhibition in combination with anti-VEGF treatment: a phase I clinical trial in non-small cell lung cancer.

BackgroundPreclinical data indicate EGFR signals through both kinase-dependent and independent pathways and that combining a small-molecule EGFR inhibitor, EGFR antibody, and/or anti-angiogenic agent is synergistic in animal models.MethodsWe conducted a dose-escalation, phase I study combining erlotinib, cetuximab, and bevacizumab. The subset of patients with non-small cell lung cancer (NSCLC) was analyzed for safety and response.ResultsThirty-four patients with NSCLC (median four prior therapies) received treatment on a range of dose levels. The most common treatment-related grade ≥2 adverse events were rash (n=14, 41%), hypomagnesemia (n=9, 27%), and fatigue (n=5, 15%). Seven patients (21%) achieved stable disease (SD) ≥6 months, two achieved a partial response (PR) (6%), and two achieved an unconfirmed partial response (uPR) (6%) (total=32%). We observed SD≥6 months/PR/uPR in patients who had received prior erlotinib and/or bevacizumab, those with brain metastases, smokers, and patients treated at lower dose levels. Five of 16 patients (31%) with wild-type EGFR experienced SD≥6 months or uPR. Correlation between grade of rash and rate of SD≥6 months/PR was observed (p less than 0.01).ConclusionThe combination of erlotinib, cetuximab, and bevacizumab was well-tolerated and demonstrated antitumor activity in heavily pretreated patients with NSCLC

A Heuristically Optimized Complex Event Processing Engine for Big Data Stream Analytics

This paper describes a Big Data stream analytics platform developed within the DEWI project for processing upcoming events from wireless sensors installed in a truck. The platform consists of a Complex Event Processing (CEP) engine capable of triggering alarms from a predefined set of rules. In general these rules are characterized by multiple parameters, for which finding their opti- mal value usually yields a challenging task. In this paper we explain a methodol- ogy based on a meta-heuristic solver that is used as a wrapper to obtain optimal parametric rules for the CEP engine. In particular this approach optimizes CEP rules through the refinement of the parameters controlling their behavior based on an alarm detection improvement criterion. As a result the proposed scheme retrieves the rules parameterized in a detection-optimal fashion. Results for a cer- tain use case – i.e. fuel level of the vehicle – are discussed towards assessing the performance gains provided by our method

Numerical Solution of a Complete Formulation of Flow in a Perfusion Bone-Tissue Bioreactor Using Lattice Boltzmann Equation Method

We report the key findings from numerical solutions of a model of transport within an established perfusion bioreactor design. The model includes a complete formulation of transport with fully coupled convection-diffusion and scaffold cell attachment. It also includes the experimentally determined internal (Poly-L-Lactic Acid (PLLA)) scaffold boundary, together with the external vessel and flow-port boundaries. Our findings, obtained using parallel lattice Boltzmann equation method, relate to (i) whole-device, steady-state flow and species distribution and (ii) the properties of the scaffold. In particular the results identify which elements of the problem may be addressed by coarse grained methods such as the Darcy approximation and those which require a more complete description. The work demonstrates that appropriate numerical modelling will make a key contribution to the design and development of large scale bioreactors.Comment: 9 pages, 3 figure

Biocatalytic Synthesis of Polyglycerol Polyricinoleate: A Comparison of Different Commercial Lipases

This paper describes the studies carried out to select the most suitable lipase as catalyst for the esterification of polyglycerol with polyricinoleic acid to yield polyglicerol polyricinoleate (PGPR), a value-added, bio-based food emulsifier. The enzymes assayed were lipases from Rhizopus arrhizus, Rhizopus oryzae and Mucor javanicus, previously selected because of their suitable activity and moderate cost. First, the reaction was catalyzed by free lipases in a batch reactor and the influence of different operating conditions (initial water content, amount of enzyme and temperature) on the progress of the reaction was studied. Next, the three lipases were immobilized by physical adsorption on the anion exchange resin, Lewatit MonoPlus MP 64, providing derivatives with a high activity and stability. Recovery of the immobilized derivative from the reaction medium was conducted with very good yields (≥ 99 %) and no loss of activity of the derivative with successive uses was proved. Finally, a high performance reactor, operating at low pressure and a dry atmosphere, was used to synthesise PGPR using the immobilized enzymes. Both Rhizopus arrhizus and Rhizopus oryzae lipases allowed the production of a PGPR which fulfils the “specific purity criteria on food additives other than colours and sweeteners” established by the Commission of the European Communities (AV ≤ 6 mg KOH/g), with an acid value of 4.91 and 5.31 mg KOH/g respectively

Structural Diversity and Biological Potential of Alkaloids from the Genus Hippeastrum, Amaryllidaceae: an Update

The subfamily Amaryllidoideae, Amaryllidaceae, presents an exclusive group of structures known as Amaryllidaceae alkaloids, which have a broad spectrum of biological activities. These plants are classified into 59 genera, including Hippeastrum Herb., which comprises approximately 60 species distributed mainly in South America, being widely used as ornamental plants due to the beauty of its flowers. This review presents an update about the alkaloid profiling of Hippeastrum extracts published between 2012 and 2021, as well as an approach to the biological potential of these compounds. Supplementary information: The online version contains supplementary material available at 10.1007/s43450-021-00211-z. Keywords: Alzheimer's disease; Anti-inflammatory; Antiparasitic; Antitumoral; Cytotoxic; Isoquinoline alkaloids

Identification of Alkaloids from Hippeastrum aulicum (Ker Gawl.) Herb.(Amaryllidaceae) Using CGC-MS and Ambient Ionization Mass Spectrometry (PS-MS and LS-MS)

Amaryllidaceae alkaloids are well-known isoquinolines which have demonstrated a wide range of biological activities such as antiviral, anticancer, acetylcholinesterase inhibition, antimalarial, among others. Mass spectrometry (MS) studies based on capillary gas chromatography (CGC), paper spray (PS), and leaf spray (LS) ionization were carried out for alkaloid investigation of the native Brazilian species Hippeastrum aulicum, along with nuclear magnetic resonance (NMR) techniques. Thirty-one alkaloids were identified including the new compound haemanthamine N-oxide. The results from PS- and LS-MS techniques were consistent with those observed in CGC-MS analysis. To the best of our knowledge, it is the first study combining NMR, CGC-MS and the ambient ionization-mass spectrometry (PS- and LS-MS) on Amaryllidaceae plants